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Updated: Jul 28, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
The structural basis of localization and signaling by the focal adhesion targeting domain
Stefan T Arold1, Maria K Hoellerer, Martin E M Noble
1Laboratory of Molecular Biophysics, University of Oxford, United Kingdom.
Abstract:
The localization of focal adhesion kinase (FAK) to sites of integrin clustering initiates downstream signaling. The C-terminal focal adhesion targeting (FAT) domain causes this localization by interacting with talin and paxillin. FAT also mediates signaling through Grb2 via phosphorylated Y925. We report two crystal structures of the FAT domain. Large rearrangements of the structure are indicated to allow phosphorylation of Y925 and subsequent interaction with Grb2. Sequence homology and structural compatibility suggest a FAT-like fold for the C-terminal domains of CAS, Efs/Sin, and HEF1. A structure-based alignment including these proteins and the vinculin tail domain reveals a conserved region that could play a role in focal adhesion targeting. Previously postulated "paxillin binding subdomains" may contribute to structural integrity rather than directly to paxillin binding.
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